EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, DECEMBER 20, 2016

Media Advisory: To contact the U.S. Preventive Services Task Force, email the Media Coordinator at Newsroom@USPSTF.net or call 202-572-2044.

To place an electronic embedded link to this report in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16776

JAMA

The U.S. Preventive Services Task Force (USPSTF) recommends against routine serologic screening (via a blood test) for genital herpes simplex virus infection in asymptomatic adolescents and adults, including those who are pregnant. The report appears in the December 20 issue of JAMA.

This is a D recommendation, indicating that there is moderate or high certainty that the screening has no net benefit or that the harms outweigh the benefits.

Genital herpes is a prevalent sexually transmitted infection in the United States; the Centers for Disease Control and Prevention estimates that almost 1 in 6 persons ages 14 to 49 years have genital herpes. Genital herpes infection is caused by 2 subtypes of herpes simplex virus (HSV), HSV-1 and HSV-2. Unlike other infections for which screening is recommended, HSV infection may not have a long asymptomatic period during which screening, early identification, and treatment may alter its course. Antiviral medications may provide symptomatic relief from outbreaks; however, these medications do not cure HSV infection. Although transmission of HSV can occur between an infected pregnant woman and her infant during vaginal delivery, interventions can help reduce transmission.

To update its 2005 recommendation on screening for genital herpes, the USPSTF reviewed the evidence on the accuracy, benefits, and harms of serologic screening for HSV-2 infection in asymptomatic persons, including those who are pregnant, as well as the effectiveness and harms of preventive medications and behavioral counseling interventions to reduce future symptomatic episodes and transmission to others.

The USPSTF is an independent, volunteer panel of experts that makes recommendations about the effectiveness of specific preventive care services such as screenings, counseling services, and preventive medications.

Detection

In the past, most cases of genital herpes in the United States have been caused by infection with HSV-2. Adequate evidence suggests that the most widely used, currently available serologic screening test for HSV-2 approved by the U.S. Food and Drug Administration is not suitable for population-based screening, based on its low specificity, the lack of widely available confirmatory testing, and its high false-positive rate. Rates of genital herpes due to HSV-1 infection in the United States may be increasing. While HSV-1 infection can be identified by serologic tests, the tests cannot determine if the site of infection is oral or genital; thus, these serologic tests are not useful for screening for asymptomatic genital herpes resulting from HSV-1 infection.

Benefits of Early Detection and Intervention

Based on limited evidence from a small number of trials on the potential benefit of screening and interventions in asymptomatic populations and an understanding of the natural history and epidemiology of genital HSV infection, the USPSTF concluded that the evidence is adequate to bound the potential benefits of screening in asymptomatic adolescents and adults, including those who are pregnant, as no greater than small.

Harms of Early Detection and Intervention

Based on evidence on potential harms from a small number of trials, the high false-positive rate of the screening tests, and the potential anxiety and disruption of personal relationships related to diagnosis, the USPSTF found that the evidence is adequate to bound the potential harms of screening in asymptomatic adolescents and adults, including those who are pregnant, as at least moderate.

Summary

Based on the natural history of HSV infection, its epidemiology, and the available evidence on the accuracy of serologic screening tests, the USPSTF concluded that the harms outweigh the benefits of serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant.

(doi:10.1001/jama.2016.16776; the full report is available pre-embargo to the media at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, DECEMBER 20, 2016

Media Advisory: To contact Anna Wald, M.D., M.P.H., email Susan Gregg at sghanson@uw.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.18189

JAMA

In a study appearing in the December 20 issue of JAMA, Anna Wald, M.D., M.P.H., of the University of Washington & Fred Hutchinson Cancer Research Center, Seattle, and colleagues compared the medications pritelivir and valacyclovir for reducing genital herpes simplex virus shedding and lesions in persons with recurrent genital herpes.

The treatment for genital herpes simplex virus (HSV) infections relies on the nucleoside analogues acyclovir, valacyclovir, or famciclovir administered either for each recurrence or daily to prevent recurrences. In addition, valacyclovir, when taken daily has been shown to reduce the risk of HSV-2 transmission to susceptible partners. However, the protection is only partial (approximately 50 percent), likely because these drugs neither completely inhibit genital viral shedding (when the virus is active and potentially transmissible to sexual partners). Alternative agents to treat HSV infections are needed.

For this crossover study, 91 participants (adults with 4 to 9 annual genital HSV-2 recurrences) were randomly assigned, 45 to receive pritelivir first, a different class of medication for genital herpes, and 46 to receive valacyclovir first. Participants took the first drug for 28 days followed by 28 days of washout before taking the second drug for 28 days. Throughout treatment, the participants collected genital swabs 4 times daily for HSV testing. The U.S. Food and Drug Administration placed the trial on clinical hold based on findings in a concurrent nonclinical toxicity study, and the sponsor terminated the study.

Of the 91 randomized participants, 56 had completed both treatment periods at the time of the study’s termination. In intent-to-treat analyses, HSV shedding was detected in 2.4 percent of swabs during pritelivir treatment compared with 5.3 percent during valacyclovir treatment. Genital lesions were present on 1.9 percent of days in the pritelivir group vs 3.9 percent in the valacyclovir group. The frequency of shedding episodes did not differ by group. Quantity of virus shed was decreased significantly during pritelivir treatment compared with valacyclovir treatment. The frequency of pain was reduced in the pritelivir group compared to the valacyclovir group.

Treatment-emergent adverse events occurred in 62 percent of participants in the pritelivir group and 69 percent of participants in the valacyclovir group.

“Further research is needed to assess longer-term efficacy and safety,” the authors write.

(doi:10.1001/jama.2016.18189; the study is available pre-embargo at the For the Media website)

Editor’s Note: This study was supported by AiCuris GmbH & Co KG. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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RELEASED: DECEMBER 13, 2016

Media Advisory: To contact Margaret A. Honein, Ph.D., email Belsie Gonzalez at Media@cdc.gov.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.19006

JAMA

Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6 percent overall had a fetus or infant with evidence of a Zika-related birth defect, and among women with first-trimester Zika infection, 11 percent had a fetus or infant with a birth defect, findings that support the importance of screening pregnant women for Zika virus exposure, according to a study published online by JAMA.

Zika virus infection during pregnancy can cause microcephaly and brain abnormalities; however, the magnitude of risk is unknown. Understanding the risk of birth defects may help guide communication, prevention, and planning efforts. Margaret A. Honein, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues estimated the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. The study included completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the U.S. Zika Pregnancy Registry (USZPR), a collaboration between the CDC and state and local health departments.

Among 442 completed pregnancies in women (median age, 28 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6 percent) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6 percent) pregnant asymptomatic women and 10 of 167 (6 percent) symptomatic pregnant women.

Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly. Infants with microcephaly (18/442) represent 4 percent of completed pregnancies. Birth defects were reported in 9 of 85 (11 percent) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or trimesters.

The authors write that based on data from population-based birth defects surveillance programs for 2009-2013, the median prevalence of microcephaly in the United States was approximately 7 per 10,000 live births.  Among completed pregnancies in the USZPR, 4 percent had a finding of microcephaly, a prevalence that is substantially higher than the background prevalence of microcephaly.

The researchers add that the findings in this report emphasize the need for pregnant women to avoid travel to areas with active Zika virus transmission and consistently and correctly use condoms to prevent sexual transmission throughout pregnancy if their partner has recently traveled to an area of active Zika virus transmission.

The CDC’s guidelines recommend “Zika virus testing for all women with possible exposure during pregnancy, regardless of symptoms. The findings that there were similar proportions with birth defects among those with symptomatic and asymptomatic maternal infections supports the importance of screening all pregnant women for Zika virus exposure and testing in accordance with CDC guidance,” the authors write.

(doi:10.1001/jama.2016.19006; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, DECEMBER 13, 2016

Media Advisory: To contact Christopher J. L. Murray, M.D., D.Phil., email Kayla Albrecht at albrek7@uw.edu.

Video Content: There is a JAMA Report video for this study, and it will be available under embargo at this link at 2 p.m. ET Friday, December 9, and include broadcast-quality downloadable video files, B-roll, scripts and other images. Please email JAMAReport@synapticdigital.com with any questions.

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JAMA

In an analysis of U.S. cause-specific county-level mortality rates from 1980 through 2014, there were large between-county differences for every cause of death, although geographic patterns varied substantially by cause of death, according to a study appearing in the December 13 issue of JAMA.

Among counties within the United States, relatively little is known about geographic patterns and inequalities in mortality by underlying cause of death. Information about variation in cause-specific mortality could provide important insights into geographic inequalities and divergent trends in life expectancy.

Christopher J. L. Murray, M.D., D.Phil., of the Institute for Health Metrics and Evaluation, University of Washington, Seattle, and colleagues used death registration data from the National Vital Statistics System to estimate annual county-level mortality rates for 21 causes of death. These estimates were raked (scaled along multiple dimensions) to ensure consistency between causes and with existing national-level estimates. Geographic patterns in the age-standardized mortality rates in 2014 and in the change in the age-standardized mortality rates between 1980 and 2014 for the 10 highest-burden causes were determined.

A total of 80,412,524 deaths were recorded from January 1, 1980, through December 31, 2014, in the United States. Of these, 19.4 million deaths were assigned garbage codes (implausible or insufficiently specific cause of death codes). Mortality rates were analyzed for 3,110 counties or groups of counties. Large between-county disparities were evident for every cause, with the gap in age-standardized mortality rates between counties in the 90th and 10th percentiles varying from 14 deaths per 100,000 population (cirrhosis and chronic liver diseases) to 147 deaths per 100,000 population (cardiovascular diseases). Geographic regions with elevated mortality rates differed among causes: for example, cardiovascular disease mortality tended to be highest along the southern half of the Mississippi River, while mortality rates from self-harm and interpersonal violence were elevated in southwestern counties, and mortality rates from chronic respiratory disease were highest in counties in eastern Kentucky and western West Virginia.

Counties also varied widely in terms of the change in cause-specific mortality rates between 1980 and 2014. For most causes (e.g., neoplasms, neurological disorders, and self-harm and interpersonal violence), both increases and decreases in county-level mortality rates were observed.

“Geographic patterns differed significantly across causes, underscoring the importance of considering cause-specific mortality in addition to measures of all-cause mortality such as life expectancy. For some causes (e.g., cardiovascular diseases), counties in the south and Appalachia had elevated mortality, while counties in western states had mortality much lower than average, a pattern that, broadly speaking, has also been documented in maps of life expectancy as well as maps of risk factors such as smoking, physical inactivity, and obesity. However, other causes had very different geographic patterns. Moreover, for some causes (e.g., mental and substance use disorders), there were striking clusters of counties with very high mortality rates. Geographic patterns in changes over time were similarly variable among causes,” the authors write.

“There are a number of potential uses for these estimates: state and county health departments could use county-level mortality estimates to identify pressing local needs and to tailor policies and programs accordingly; physicians could use these estimates to better understand the health concerns of the populations they serve; researchers could identify counties that have done unexpectedly well or poorly with regard to a particular cause of death and that warrant additional study to identify factors driving these trends; and communities can use these estimates as evidence when advocating for change. Further, for causes of death for which effective treatments are available, variation in mortality rates can highlight where access to treatment or quality of care is a pressing problem.”

(doi:10.1001/jama.2016.13645; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was funded by a grant from the Robert Wood Johnson Foundation and the National Institute on Aging, and a philanthropic gift from John W. Stanton and Theresa E. Gillespie. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, DECEMBER 6, 2016

Media Advisory: To contact Douglas A. Mata, M.D., M.P.H., email Elaine St. Peter at estpeter@partners.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.17324

JAMA

A review and analysis of nearly 200 studies involving 129,000 medical students in 47 countries found that the prevalence of depression or depressive symptoms was 27 percent, that 11 percent reported suicidal ideation during medical school, and only about 16 percent of students who screened positive for depression reportedly sought treatment, according to a study appearing in the December 6 issue of JAMA, a medical education theme issue.

Studies have suggested that medical students experience high rates of depression and suicidal ideation; however, prevalence estimates vary across studies. Reliable estimates of depression and suicidal ideation prevalence during medical training are important for informing efforts to prevent, treat, and identify causes of emotional distress among medical students, especially in light of recent work revealing a high prevalence of depression in resident physicians.

Douglas A. Mata, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues conducted a systematic review and meta-analysis of published studies of depression, depressive symptoms, and suicidal ideation in undergraduate medical trainees. The researchers identified 195 studies that met criteria for inclusion in the analysis.

Depression or depressive symptom prevalence data were extracted from 167 cross-sectional studies (n = 116,628) and 16 longitudinal studies (n = 5,728) from 43 countries. The overall pooled crude prevalence of depression or depressive symptoms was 27 percent (37,933/122,356 individuals). Summary prevalence estimates ranged across assessment methods from 9 percent to 56 percent. Depressive symptom prevalence remained relatively constant over the period studied (baseline survey year range of 1982-2015). In the 9 longitudinal studies that assessed depressive symptoms before and during medical school, the median absolute increase in symptoms was 14 percent. Prevalence estimates did not significantly differ between studies of only preclinical students and studies of only clinical students (23.7 percent vs 22.4 percent). The percentage of medical students screening positive for depression who sought psychiatric treatment was 16 percent (110/954 individuals).

Suicidal ideation prevalence data were extracted from 24 cross-sectional studies (n = 21,002) from 15 countries. The overall pooled crude prevalence of suicidal ideation was 11 percent (2,043/21,002 individuals). Summary prevalence estimates ranged across assessment methods from 7 percent to 24 percent.

“The present analysis builds on recent work demonstrating a high prevalence of depression among resident physicians, and the concordance between the summary prevalence estimates (27.2 percent in students vs 28.8 percent in residents) suggests that depression is a problem affecting all levels of medical training. Taken together, these data suggest that depressive and suicidal symptoms in medical trainees may adversely affect the long-term health of physicians as well as the quality of care delivered in academic medical centers,” the authors write.

“Possible causes of depressive and suicidal symptomatology in medical students likely include stress and anxiety secondary to the competitiveness of medical school. Restructuring medical school curricula and student evaluations might ameliorate these stresses. Future research should also determine how strongly depression in medical school predicts depression during residency and whether interventions that reduce depression in medical students carry over in their effectiveness when those students transition to residency. Furthermore, efforts are continually needed to reduce barriers to mental health services, including addressing the stigma of depression.”

“Further research is needed to identify strategies for preventing and treating these disorders in this population,” the researchers conclude.

(doi:10.1001/jama.2016.17324; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, DECEMBER 6, 2016

Media Advisory: To contact Joshua L. Denson, M.D., email David Kelly at david.kelly@ucdenver.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.17424

JAMA

Among patients admitted to internal medicine services in 10 Veterans Affairs hospitals, end-of-rotation transition in care was associated with significantly higher in-hospital mortality in an unrestricted analysis that included most patients, but not in an alternative restricted analysis, according to a study appearing in the December 6 issue of JAMA, a medical education theme issue.

A handoff is defined as the transition of patient care to another clinician through the transfer of information, responsibility, and authority. Increasing evidence indicates shift-to-shift handoffs are a source of adverse events and errors, and conversely, that interventions to improve such handoffs may have meaningful benefits to patient safety. However, the association between end-of-rotation transition and adverse events is uncertain.

Joshua L. Denson, M.D., of the University of Colorado School of Medicine, Aurora, and colleagues examined the association of end-of-rotation house staff transitions with mortality among hospitalized patients. The study included patients admitted to internal medicine services at 10 university-affiliated U.S. Veterans Health Administration hospitals (2008-2014). Transition patients (defined as those admitted prior to an end-of-rotation transition who died or were discharged within 7 days following transition) were stratified by type of transition (intern only, resident only, or intern + resident) and compared with all other discharges (control). An alternative analysis comparing admissions within 2 days before transition with admissions on the same 2 days 2 weeks later was also conducted.

Among 230,701 patient discharges (average age, 66 years; median length of stay, 3 days), overall mortality was 2.2 percent in-hospital, 9.5 percent at 30 days, and 14 percent at 90 days. Adjusted hospital mortality was significantly greater in transition vs control patients for the intern-only and intern + resident groups, but not for the resident-only group. Adjusted 30-day and 90-day mortality rates were greater in all transition vs control comparisons. Accreditation Council for Graduate Medical Education (ACGME) duty-hour changes (limiting first-year residents [interns] to 16 continuous hours of work) was associated with greater adjusted hospital mortality for transition patients in the intern-only and intern + resident groups than for controls. The alternative analyses did not demonstrate any significant differences in mortality between transition and control groups. There were no significant associations with readmission rates.

“Together, these results showed that end-of­ rotation transitions in care were associated with increased mortality; however, this increased risk may be limited to longer-stay, complex patients with greater comorbidities or those discharged soon after the transition,” the authors write.

(doi:10.1001/jama.2016.17424; the study is available pre-embargo at the For the Media website)

Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, DECEMBER 6, 2016

Media Advisory: To contact Charlie M. Wray, D.O., M.S., email Matthew Coulson at Matthew.Coulson@va.gov.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.17786

JAMA

Survey responses from internal medicine residency program directors reported large variation in implementation of recommended handoff techniques and educational strategies to teach handoffs in internal medicine training programs, according to a study appearing in the December 6 issue of JAMA, a medical education theme issue.

National organizations have recommended specific strategies to improve resident handoffs, such as dedicated time and space to perform handoffs, standardized templates, and supervision by senior physicians. How these best-practice recommendations are implemented across programs is unknown. Charlie M. Wray, D.O., M.S., of the San Francisco Veterans Affairs Medical Center, and colleagues examined internal medicine residency program directors’ responses to the 2014 Association of Program Directors in Internal Medicine electronic survey, in which they were asked to report implementation of handoff strategies within 3 domains: properties of verbal handoffs (i.e., dedicated time), properties of written handoffs (i.e., use of electronic health records [EHRs]), and educational resources (i.e., didactic lectures).

Among all programs, 234 of 361 (65 percent) responded to the survey. Most program directors (61 percent) were very or somewhat satisfied with the handoff strategies used at their institutions. Implementation of handoff strategies ranged from 6 percent to 67 percent, with the most frequent strategies being dedicated time (67 percent), didactic lectures (64 percent), overlapping shifts (61 percent), ward-based teaching by residents (61 percent), and allowing the receiver access to patient records (60 percent).

Statistically significant differences in the proportion of program directors who were satisfied were observed for those implementing vs not implementing 4 strategies: having a dedicated room, supervision by a senior resident, EHR-enabled handoff, and receiver given written copy of sign out. Implementation ranged between 47 percent (EHR-enabled handoff) and 59 percent (receiver given written copy of sign out), with 12 percent implementing all 4 strategies.

“Discordance between low implementation and high program director satisfaction may indicate confusion regarding which practices are best for their setting because of the lack of strong or consistent evidence,” the authors write. “Also, program directors may want to implement these handoff strategies but face significant barriers, such as an EHR unable to facilitate shift handoffs or lack of local expertise to lead interactive workshops.”

“Future work to disseminate and implement recommended handoff strategies is warranted.”
(doi:10.1001/jama.2016.17786; the study is available pre-embargo at the For the Media website)

Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, DECEMBER 6, 2016

Media Advisory: To contact Lisa M. Meeks, Ph.D., email Laura Kurtzman at Laura.Kurtzman@ucsf.edu.

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JAMA

New research has identified a higher prevalence of disability among students in U.S. allopathic medical schools (2.7 percent) than prior studies (0.3 percent to 0.6 percent), according to a study appearing in the December 6 issue of JAMA, a medical education theme issue.

Studying the performance of medical students with disabilities requires a better understanding of the prevalence and categories of disabilities represented. It remains unclear how many medical students have disabilities; prior estimates are out-of-date and psychological, learning, and chronic health disabilities have not been evaluated. For this study, Lisa M. Meeks, Ph.D., of the University of California, San Francisco School of Medicine, and Kurt R. Herzer, Ph.D., M.Sc., of the Johns Hopkins School of Medicine, Baltimore, assessed the prevalence of all disabilities and the accommodations in use at allopathic medical schools in the United States.

From December 2014 through February 2016, an electronic, web-based survey was sent to institutionally designated disability administrators at eligible allopathic medical schools who have a federally mandated duty to assist qualified students with disabilities. The survey was designed by experts in medical school disability administration based on provisions of the Americans with Disabilities Act and prior research. The survey assessed the following domains: (1) total number of self-disclosed or registered students with disabilities receiving accommodations, (2) demographic characteristics of students with disabilities, (3) categories of disabilities, and (4) approved accommodations.

One hundred forty-five schools were identified; 12 were excluded. Of the 133 eligible schools, 91 completed the survey (68 percent) and 89 reported complete data and were included in the analysis. Respondents identified 1,547 students with disabilities (43 percent male), representing 2.7 percent of the total enrollment and ranging from 0 percent to 12 percent. Of these students, 98 percent received accommodations. Attention-deficit/hyperactivity disorder (ADHD) was the most common disability (34 percent), followed by learning disabilities (22 percent) and psychological disabilities (20 percent). Mobility and sensory disabilities were less common. School-based testing accommodations were most frequently used (98 percent); clinical accommodations were less frequently used.

“These results underscore the limitations of studying isolated subtypes of disabilities (i.e., only mobility impairments), which may underestimate this population. The preponderance of students with ADHD, learning disabilities, and psychological disabilities suggests that these disability subtypes should be included in future research efforts, such as studies assessing the performance of appropriately accommodated students,” the authors write.

(doi:10.1001/jama.2016.10544; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was supported by a grant from the National Institute of General Medical Sciences’ Medical Scientist Training Program and from the National Institute on Aging. Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) THURSDAY, DECEMBER 1, 2016

Media Advisory: To contact Hope S. Rugo, M.D., email Elizabeth Fernandez at Elizabeth.Fernandez@UCSF.edu. To contact Howard Bauchner, M.D., email Jim Michalski at jim.michalski@jamanetwork.org. To contact Deborah Schrag, M.D., M.P.H., email John Noble at johnw_noble@dfci.harvard.edu.

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Among women with metastatic breast cancer, treatment with a drug that is biosimilar to the breast cancer drug trastuzumab resulted in an equivalent overall response rate at 24 weeks compared with trastuzumab, according to a study published online by JAMA.

Biological agents, including monoclonal antibodies, have increased the treatment options and greatly improved outcomes for a number of cancers. However, patient access to these biologics is limited in many countries. With impending patent expiration of some biological agents, development of biosimilars has become a high priority for drug developers and health authorities throughout the world to provide access to high-quality alternatives. A biosimilar drug is a biological product that is highly similar to a licensed biological product, with no clinically meaningful differences in terms of safety or potency.

Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves progression-free and overall survival in patients with ERBB2 (HER2)-positive metastatic breast cancer. In this multicenter, phase 3 study, Hope S. Rugo, M.D., of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and colleagues randomly assigned patients with ERBB2-positive metastatic breast cancer to receive a proposed trastuzumab biosimilar (MYL-14010) (n = 230) or trastuzumab (n = 228) with a taxane (a chemotherapy agent) to compare the overall response rate and safety after 24 weeks. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred. Tumor was assessed every 6 weeks. The primary outcome was week 24 overall response rate defined as complete or partial response.

The overall response rate was 70 percent for the proposed biosimilar vs 64 percent for trastuzumab. At week 48, there was no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41 percent vs 43 percent), progression-free survival (44 percent vs 45 percent), or overall survival (89 percent vs 85 percent). In the proposed biosimilar and trastuzumab groups, 99 percent and 95 percent of patients had at least 1 adverse event.

“Trastuzumab is not widely available around the world,” the authors write. “A biosimilar treatment option may increase global access to biologic cancer therapies, provided, among other issues, that the price of the biosimilar is sufficiently inexpensive to enable women in non-high-income countries to access this therapy.”

The researchers note that further study is needed to assess safety as well as long-term clinical outcome.

(doi:10.1001/jama.2016.18305; the study is available pre-embargo at the For the Media website)

Editor’s Note: This study was funded and sponsored by Mylan Inc. and Biocon Research Limited. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Scientific Evidence and Financial Obligations to Ensure Access to Biosimilars for Cancer Treatment

In an accompanying editorial, Howard Bauchner, M.D., Editor in Chief, JAMA, Chicago, and colleagues write that one of the sponsors of this study, Mylan, “has recently attracted attention because of the pricing, promotion, and involvement in the health policies of schools regarding one of its products, injectable epinephrine (EpiPen). There has been substantial criticism of the company by patients, physicians, and politicians about the recent price increase and the subsequent introduction of a generic epinephrine product by the same company.”

“The proposed trastuzumab biosimilar will need to be priced at a level at which patients who otherwise would not have access to expensive therapies such as trastuzumab could receive needed therapy. In announcing their FDA submission for the proposed trastuzumab biosimilar, the sponsors of the trial by Rugo et al have expressed their ‘shared commitment to increasing access to these critical medicines worldwide’ and indicated that ‘this advancement in the U.S. will enable us to enhance access to this affordable therapy to larger patient pools.’ Ultimately, to fulfill these pledges the manufacturers must ensure that the pricing of this biosimilar product is responsible and fair and provides access to this important therapy at an affordable price.”

(doi:10.1001/jama.2016.18743; the editorial is available pre-embargo at the For the Media website)

Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Biosimilar Therapy for ERBB2 (HER2)-Positive Breast Cancer

“The greatest potential value of the proposed trastuzumab biosimilar would be facilitating access to treatment for patients with ERBB2-positive breast cancer and gastric cancer around the world who now are untreated because of prohibitive costs,” write Harold J. Burstein, M.D., Ph.D., and Deborah Schrag, M.D., M.P.H., of Harvard Medical School, Boston, and Associate Editor, JAMA (Dr. Schrag) in an accompanying editorial. “Unless the price of the trastuzumab biosimilar is set considerably lower than the 25 percent to 30 percent discounts typically seen during the last decade for biosimilars entering European markets, treatment will remain inaccessible for far too many patients.”

This study “opens the pathway to therapeutic biosimilars in oncology and should facilitate market forces that lead to lower drug prices. Hopefully, this competition will be sufficient to make trastuzumab and other biologics more affordable and thereby make cancer care both more effective and more equitable around the world.”

(doi:10.1001/jama.2016.18979; the editorial is available pre-embargo at the For the Media website)

Editor’s Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 29, 2016

Media Advisory: To contact Lily Peng, M.D., Ph.D., email Charina Choi at charinac@google.com.

Related material: Also available at the For the Media website, the editorial, “Artificial Intelligence With Deep Learning Technology Looks Into Diabetic Retinopathy Screening,” by Tien Yin Wong, M.D., Ph.D., of the Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, and Neil M. Bressler, M.D., of Johns Hopkins University, Baltimore, and Editor, JAMA Ophthalmology; the editorial, “Translating Artificial Intelligence Into Clinical Care,” by Andrew L. Beam, Ph.D., and Isaac S. Kohane, M.D., Ph.D., of Harvard Medical School, Boston; and the Viewpoint, “Adapting to Artificial Intelligence,” by Saurabh Jha, M.B.B.S., M.R.C.S., M.S., of the University of Pennsylvania, Philadelphia, and Eric J. Topol, M.D., of Scripps Research Institute, La Jolla, Calif.

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JAMA

In an evaluation of retinal photographs from adults with diabetes, an algorithm based on deep machine learning had high sensitivity and specificity for detecting referable diabetic retinopathy, according to a study published online by JAMA.

Among individuals with diabetes, the prevalence of diabetic retinopathy is approximately 29 percent in the United States. Most guidelines recommend annual screening for those with no retinopathy or mild diabetic retinopathy and repeat examination in 6 months for moderate diabetic retinopathy. Retinal photography with manual interpretation is a widely accepted screening tool for diabetic retinopathy.

Automated grading of diabetic retinopathy has potential benefits such as increasing efficiency and coverage of screening programs; reducing barriers to access; and improving patient outcomes by providing early detection and treatment. To maximize the clinical utility of automated grading, an algorithm to detect referable diabetic retinopathy is needed. Machine learning (a discipline within computer science that focuses on teaching machines to detect patterns in data) has been leveraged for a variety of classification tasks including automated classification of diabetic retinopathy. However, much of the work has focused on “feature-engineering,” which involves computing explicit features specified by experts, resulting in algorithms designed to detect specific lesions or predicting the presence of any level of diabetic retinopathy. Deep learning is a machine learning technique that avoids such engineering and allows an algorithm to program itself by learning the most predictive features directly from the images given a large data set of labeled examples, removing the need to specify rules explicitly. Application of these methods to medical imaging requires further assessment and validation.

In this study, Lily Peng, M.D., Ph.D., of Google Inc., Mountain View, Calif., and colleagues applied deep learning to create an algorithm for automated detection of diabetic retinopathy and diabetic macular edema in retinal fundus (the interior lining of the eyeball, including the retina, optic disc, and the macula) photographs. A specific type of network optimized for image classification was trained using a data set of 128,175 retinal images, which were graded 3 to 7 times for diabetic retinopathy, diabetic macular edema, and image gradability by a panel of 54 U.S. licensed ophthalmologists and ophthalmology senior residents between May and December 2015. The resultant algorithm was validated using 2 separate data sets (EyePACS-1, Messidor-2), both graded by at least 7 U.S. board-certified ophthalmologists.

The EyePACS-1 data set consisted of 9,963 images from 4,997 patients (prevalence of referable diabetic retinopathy [RDR; defined as moderate and worse diabetic retinopathy, referable diabetic macular edema, or both], 8 percent of fully gradable images; the Messidor-2 data set had 1,748 images from 874 patients (prevalence of RDR, 15 percent of fully gradable images). Use of the algorithm achieved high sensitivities (97.5 percent [EyePACS-1] and 96 percent [Messidor-2]) and specificities (93 percent and 94 percent, respectively) for detecting referable diabetic retinopathy.

“These results demonstrate that deep neural networks can be trained, using large data sets and without having to specify lesion-based features, to identify diabetic retinopathy or diabetic macular edema in retinal fundus images with high sensitivity and high specificity. This automated system for the detection of diabetic retinopathy offers several advantages, including consistency of interpretation (because a machine will make the same prediction on a specific image every time), high sensitivity and specificity, and near instantaneous reporting of results,” the authors write.

“Further research is necessary to determine the feasibility of applying this algorithm in the clinical setting and to determine whether use of the algorithm could lead to improved care and outcomes compared with current ophthalmologic assessment.”

(doi:10.1001/jama.2016.17216; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

EMBARGOED FOR RELEASE: 11 A.M. (ET) MONDAY, NOVEMBER 21, 2016

Media Advisory: To contact Ole-Erik Iversen, M.D., Ph.D., email Ole-Erik.Iversen@uib.no. To contact editorial co-author Lauri E. Markowitz, M.D., email CDC Media Relations at media@cdc.gov.

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In a study published online by JAMA, Ole-Erik Iversen, M.D., Ph.D., of the University of Bergen, Norway, and colleagues examined whether human papillomavirus (HPV) type-specific antibody responses would be noninferior (not worse than) among girls and boys ages 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women ages 16 to 26 years who received the standard 3 doses.

For this study, conducted at 52 ambulatory care sites in 15 countries, five groups were enrolled:(1) girls ages 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys ages 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys ages 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls ages 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women ages 16 to 26 years to receive 3 doses over 6 months (n = 314).

Of the 1,518 participants (753 girls [average age, 11.4 years]; 451 boys [average age, 11.5 years]; and 314 adolescent girls and young women [average age, 21 years]), 1,474 completed the study and data from 1,377 were analyzed. At 4 weeks after the last dose, the researchers found that HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses.

“Diseases related to the human papillomavirus impose a substantial health care burden on both the developing and developed world,” the authors write. “In many countries, HPV vaccination rates remain suboptimal. Using an effective 2-dose regimen entailing fewer visits could improve adherence to HPV vaccination programs. Co-administration of the 9-valent HPV vaccine with diphtheria, tetanus, pertussis, polio, and meningococcal vaccines could also be completed at the same visit, which has been demonstrated in clinical studies. Based on health economics modeling, use of a 2-dose vaccination schedule could potentially reduce the total costs of HPV vaccination.”

“Further research is needed to assess persistence of antibody responses and effects on clinical outcomes.”

(doi:10.1001/jama.2016.17615; the study is available pre-embargo at the For the Media website)

Editor’s Note: The study was sponsored and funded by Merck & Co, which manufactures the quadrivalent and nonavalent HPV vaccines. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Two vs Three Doses of Human Papillomavirus Vaccine

“In October 2016, the CDC recommended a 2-dose schedule for adolescents starting the HPV vaccination series before the age of 15 years. This important policy change for the United States is supported by previously published data as well as results from the clinical trial by Iversen and colleagues in this issue of JAMA. This clinical trial, which included 1,518 participants, was the basis for the recent approval from the Food and Drug Administration of a 2-dose series of the 9-valent HPV vaccine for adolescents,” writes Lauri E. Markowitz, M.D., of the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues in an accompanying editorial. “With data from the trial reported in JAMA, evidence now supports a 2-dose schedule in adolescents (aged 9 to 14 years) for all 3 licensed HPV vaccines.”

“During the first decade of the HPV vaccination program, knowledge has increased about these highly effective HPV vaccines. Population-level effects of vaccination programs on infection and disease outcomes have exceeded expectations in many countries, and extensive safety evaluations have not identified concerns. In the second decade, reduced dose schedules might help achieve higher HPV vaccination coverage, advance HPV vaccine program introductions in more countries, and further reduce the burden of HPV-associated cancers and disease worldwide.”

(doi:10.1001/jama.2016.16393; the study is available pre-embargo at the For the Media website)

Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 22, 2016

Media Advisory: To contact Dio Kavalieratos, Ph.D., email Lawerence Synett at synettl@upmc.edu. To contact Preeti N. Malani, M.D., M.S.J., email Shantell Kirkendoll at smkirk@umich.edu.

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In a study appearing in the November 22/29 issue of JAMA, Dio Kavalieratos, Ph.D., of the University of Pittsburgh, and colleagues examined the association of palliative care with quality of life, symptom burden, survival, and other outcomes for people with life-limiting illness and for their caregivers.

Palliative care focuses on improving quality of life (QOL) and reducing suffering for seriously ill patients and their families. More than 65 percent of U.S. hospitals have an inpatient palliative care program. To provide an up-to-date summary of palliative care outcomes, the authors identified 43 randomized clinical trials of palliative care interventions in adults with life-limiting illness for a systematic review and meta-analyses. The trials provided data on 12,731 patients (average age, 67 years) and 2,479 caregivers. Thirty-five trials used usual care as the control, and 14 took place in the ambulatory setting.

In the meta-analysis, palliative care was associated with statistically and clinically significant improvements in measures of patient QOL and symptom burden at the 1- to 3-month follow-up. When analyses were limited to trials at low risk of bias (n = 5), the association between palliative care and QOL was lessened but remained statistically significant, whereas the association with symptom burden was not statistically significant. There was no association between palliative care and survival. Findings for caregiver outcomes were inconsistent.

Palliative care was associated consistently with improvements in advance care planning, patient and caregiver satisfaction, and lower health care utilization.  There was mixed evidence of associations of palliative care with site of death; patient mood; health care expenditures; and caregiver QOL, mood, or burden.

The authors write that future research should aim to identify the efficacious component(s) of palliative care.

(doi:10.1001/jama.2016.16840; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: The Promise of Palliative Care

In an accompanying editorial, Preeti N. Malani, M.D., M.S.J., of the University of Michigan Health System, Ann Arbor, and Associate Editor, JAMA, and Eric Widera, M.D., of the University of California, San Francisco, write that “along with a growing list of studies demonstrating benefit of palliative care, there is an imperative to train both specialists and nonspecialists to deliver interventions proven to be effective.”

“A multipronged approach, such as the Palliative Care and Hospice Education and Training Act (PCHETA), provides a road map for how to accomplish this goal. Along with expanding palliative care research and public awareness, PCHETA is designed to establish a nationwide network of palliative care and hospice education centers that could expand specialist training programs and also train all clinicians in providing high-quality palliative care. With estimated expenditures of up to $49.1 million per year, the cost of PCHETA is small compared with the potential benefits of meaningfully improving the quality of life of individuals living with serious illness.”

(doi:10.1001/jama.2016.17163; the editorial is available pre-embargo at the For the Media website)

Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Widera reports that he is a board member of the American Academy of Hospice and Palliative Care Medicine. No other disclosures were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 22, 2016

Media Advisory: To contact co-author Daniel S. Budnitz, M.D., M.P.H., email CDC Media Relations at media@cdc.gov. To contact editorial co-author Chad Kessler, M.D., M.H.P.E., email Sarah Avery at sarah.avery@duke.edu.

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The prevalence of emergency department visits for adverse drug events in the United States was estimated to be 4 per 1,000 individuals in 2013 and 2014, and the most common drug classes involved were anticoagulants, antibiotics, diabetes agents, and opioid analgesics, according to a study appearing in the November 22/29 issue of JAMA.

Adverse drug events have recently received attention in national patient safety initiatives. The Patient Protection and Affordable Care Act of 2010 incentivized new programs that target adverse drug event prevention within hospitals and during care transitions between inpatient and outpatient settings. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts.

Nadine Shehab, Pharm.D., M.P.H., of the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues examined characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and changes in ED visits for adverse drug events since 2005-2006. The researchers analyzed nationally representative data from 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project.

Based on data from 42,585 cases, an estimated four ED visits for adverse drug events occurred per 1,000 individuals annually in 2013 and 2014, and 27 percent of ED visits for adverse drug events resulted in hospitalization. An estimated 35 percent of ED visits for adverse drug events occurred among adults ages 65 years or older in 2013-2014 compared with an estimated 26 percent in 2005-2006; older adults experienced the highest hospitalization rates (44 percent).

Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 47 percent of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased.

Among children ages 5 years or younger, antibiotics were the most common drug class implicated (56 percent). Among children and adolescents ages 6 to19 years, antibiotics also were the most common drug class implicated (32 percent) in ED visits for adverse drug events, followed by antipsychotics (4.5 percent).

Among older adults (65 years and older), three drug classes (anticoagulants, diabetes agents, and opioid analgesics) were implicated in an estimated 60 percent of ED visits for adverse drug events; four anticoagulants (warfarin, rivaroxaban, dabigatran, and enoxaparin) and five diabetes agents (insulin and 4 oral agents) were among the 15 most common drugs implicated. Medications to always avoid in older adults according to certain criteria (“Beers criteria”) were implicated in 1.8 percent of ED visits for adverse drug events.

“Targeting adverse drug events common among specific patient populations, such as among the youngest (age 19 years or less) and oldest (age 65 years and older), may help further focus outpatient medication safety efforts,” the authors write.

(doi:10.1001/jama.2016.16201; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Reducing Adverse Drug Events

“The question remains how to best leverage the existing system to improve the safety of the process of starting, monitoring, and discontinuing medications,” writes Chad Kessler, M.D., M.H.P.E., of the Durham VA Medical Center, Durham, N.C., and colleagues in an accompanying editorial.

“Collaboration is needed among physicians and other health professionals in primary care, specialty care, pharmacy, and emergency medicine to answer these questions in the quest for safer models of patient care. Furthermore, this collaboration across health care locations and the continuum of care will affect how much benefit or harm patients receive from prescribed medications. Integrated health care systems can help lead the way through improved care coordination and transition of care models. The work by Shehab et al shines a spotlight on the problem of adverse drug events and highlights the need to address this important clinical issue in a more systematic and organized fashion.”

(doi:10.1001/jama.2016.16392; the editorial is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 22, 2016

Media Advisory: To contact Areej El-Jawahri, M.D., email Katie Marquedant at kmarquedant@partners.org.

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Among patients with hematologic malignancies undergoing hematopoietic stem cell transplantation, the use of inpatient palliative care compared with standard transplant care resulted in a smaller decrease in quality of life two weeks after transplantation, according to a study appearing in the November 22/29 issue of JAMA.

Patients with hematologic malignancies hospitalized for hematopoietic stem cell (“bone marrow”) transplantation (HCT) experience physical symptoms due to chemotherapy-induced toxic effects and early post-transplantation complications. These symptoms, along with the physical isolation patients experience during the 3- to 4-week hospitalization, can contribute to a decline in their quality of life (QOL) throughout their hospital stay. Despite the physical and psychological burden experienced by patients undergoing HCT, studies of interventions to improve their QOL and reduce their distress during HCT are limited. Although palliative care clinicians are increasingly asked to care for patients with solid tumors, they are infrequently consulted for patients with hematologic malignancies.

Areej El-Jawahri, M.D., of Massachusetts General Hospital, Boston and colleagues randomly assigned 160 adults with hematologic malignancies undergoing HCT and their caregivers to the intervention (n=81; patients were seen by palliative care clinicians at least twice a week during HCT hospitalization; the intervention was focused on management of physical and psychological symptoms), or standard transplant care (n=79). Patients receiving standard care could be seen by palliative care clinicians on request.

Among the patients (average age, 60 years; 57 percent women), 98 percent completed 2-week follow-up; 93 percent completed 3-month follow-up. The researchers found that intervention patients reported a smaller decrease on measures of QOL from study entry to week 2 vs controls. Also, intervention patients had less increase in depression, lower anxiety, no difference in fatigue, and less increase in symptom burden. At 3 months, intervention patients had higher QOL, lower depression and post-traumatic stress symptoms but no significant differences in anxiety, fatigue, or symptom burden.

From baseline to week 2 after HCT, caregivers of intervention patients vs controls reported no significant differences in QOL or anxiety but had a smaller increase in depression.

“Palliative care may help to lessen the decline in QOL experienced by patients during hospitalization for HCT, which has long been perceived as a natural aspect of the transplantation process,” the authors write.

“Further research is needed for replication and to assess longer-term outcomes and cost implications.”

(doi:10.1001/jama.2016. 16786; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was supported by funds from the National Palliative Care Research Foundation and a grant from the National Cancer Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 22, 2016

Media Advisory: To contact Heidi E. Brown, Ph.D., email Gerri Kelly at gkelly@email.arizona.edu.

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In a study appearing in the November 22/29 issue of JAMA, Heidi E. Brown, Ph.D., of the University of Arizona, Tucson, and colleagues investigated trends in infectious disease mortality in the United States from 1980 through 2014.

From 1900 through 1996, mortality from infectious diseases declined in the United States, except for a 1918 spike due to the Spanish flu pandemic. Since 1996, major changes in infectious diseases have occurred, such as the introduction of human immunodeficiency virus (HIV)/AIDS and West Nile virus into the United States, advances in HIV/AIDS treatment, changes in vaccine perceptions, and increased concern over drug-resistant pathogens. To examine these changes, the authors used data from the National Office of Vital Statistics reports from 1900 through 1967 and from the Centers for Disease Control and Prevention (CDC) WONDER database from 1968 through 2014.

Overall and infectious disease mortality decreased from 1900 through 1950 (except for the 1918 spike) and then leveled off. From 1980 through 2014, infectious diseases composed 5.4 percent of overall mortality. Per 100,000 population, infectious disease mortality increased from 42 in 1980 to 64 in 1995, paralleling trends in HIV/AIDS mortality. A decline in overall and HIV/AIDS mortality in 1995 was associated with the introduction of antiretroviral therapy. Most infectious disease deaths (38 percent) from 1980 through 2014 were due to influenza or pneumonia.

Vaccine-preventable disease death rates decreased since 1980. Mortality due to hepatitis B alone showed an increase coincident with the HIV/AIDS epidemic. Mortality due to pathogens with drug-resistant strains remained stable since 1980. Mortality from Clostridium difficile, a hospital-acquired infection with drug resistance, increased from almost none in 1989 until reaching a plateau since 2007.

“Grouping related diseases (e.g., vector-borne disease) and using national-level data allow for the evaluation of general trends. However, trends in population subgroups and at the community level, such as measles outbreaks within low-vaccination communities, were not captured. Nonetheless, these trends illustrate the continued U.S. vulnerability to infectious diseases,” the authors write.

(doi:10.1001/jama.2016.12423; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3:45 P.M. (ET) TUESDAY, NOVEMBER 15, 2016

Media Advisory: To contact Maryam Kavousi, M.D., Ph.D., email m.kavousi@erasmusmc.nl.

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JAMA

Among women at low risk of atherosclerotic cardiovascular disease (ASCVD), coronary artery calcium was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors, according to a study published online by JAMA. The study is being released to coincide with its presentation at the American Heart Association’s Scientific Sessions 2016.

Cardiovascular disease (CVD) is a major health problem for women worldwide. The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low CVD risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear. Coronary artery calcium scanning allows for the detection of subclinical coronary atherosclerosis, and the presence of CAC in asymptomatic individuals is associated with higher risk for coronary heart disease (CHD) and all-cause mortality.

Maryam Kavousi, M.D., Ph.D., of Erasmus University Medical Center, Rotterdam, the Netherlands and colleagues assessed the potential utility of CAC testing (by computed tomography) for CVD risk estimation and stratification among low-risk women. The study included women with 10-year ASCVD risk lower than 7.5 percent from 5 large population-based cohorts.

Among 6,739 women with low ASCVD risk from the 5 studies, average age ranged from 44 to 63 years and CAC was present in 36 percent. Across the cohorts, median follow-up ranged from 7 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal heart attacks, 29 CHD deaths, and 72 strokes). Compared with the absence of CAC (CAC = 0), presence of CAC (CAC greater than 0) was associated with an increased risk of ASCVD. Coronary artery calcium was associated with modest improvement in prognostic accuracy compared with traditional risk factors.

“Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy,” the authors write.

“The decision regarding the use of CAC among low-risk women needs to consider the broader context and whether any additional testing is justifiable vs simply treating all such women with statins based on risk factor scores alone.”

(doi:10.1001/jama.2016.17020; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) SUNDAY, NOVEMBER 13, 2016

Media Advisory: To contact the U.S. Preventive Services Task Force, email the Media Coordinator at Newsroom@USPSTF.net or call 202-572-2044.

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The U.S. Preventive Services Task Force (USPSTF) has issued a recommendation statement regarding the use of statins for primary prevention of cardiovascular disease in adults. The report appears in the November 15 issue of JAMA.

Recommendations

• The USPSTF recommends initiating use of low- to moderate-dose statins in adults ages 40 to 75 years without a history of cardiovascular disease (CVD) who have 1 or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of 10 percent or greater (B recommendation, indicating that there is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial).

• The USPSTF recommends that clinicians selectively offer low- to moderate-dose statins to adults ages 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5 to 10 percent (C recommendation, indicating this should be selectively offered or provided to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small).

• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating statin use in adults 76 years and older (I statement, indicating that evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined).

To update its 2008 recommendation on screening for lipid disorders in adults, the USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of dyslipidemia in adults 21 years and older; the benefits and harms of statin use in reducing CVD events and mortality in adults without a history of CVD events; whether the benefits of statin use vary by subgroup, clinical characteristics, or dosage; and the benefits of various treatment strategies in adults 40 years and older without a history of CVD events.

The USPSTF is an independent, volunteer panel of experts that makes recommendations about the effectiveness of specific preventive care services such as screenings, counseling services, and preventive medications.

Importance

Cardiovascular disease is a broad term that encompasses a number of atherosclerotic conditions that affect the heart and blood vessels, including coronary heart disease, as ultimately manifested by myocardial infarction (MI; heart attack), and cerebrovascular disease, as ultimately manifested by stroke. Cardiovascular disease is the leading cause of illness and death in the United States, accounting for 1 of every 3 deaths among adults. Statins are a class of lipid-lowering medications that reduce levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C).

Potential Benefits of Statin Use

The USPSTF found adequate evidence that use of low- to moderate­ dose statins: reduces the probability of CVD events (heart attack or ischemic stroke) and mortality by at least a moderate amount in adults ages 40 to 75 years who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10 percent or greater; and reduces the probability of CVD events and mortality by at least a small amount in adults ages 40 to 75 years who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5 to 10 percent. The USPSTF found inadequate evidence to conclude whether initiating statin use in adults 76 years and older who are not already taking a statin is beneficial in reducing the incidence of CVD events and mortality.

Potential Harms of Statin Use

The USPSTF found adequate evidence that the harms of low- to moderate-dose statin use in adults aged 40 to 75 years are small. The USPSTF found inadequate evidence on the harms of initiating statin use for the prevention of CVD events in adults 76 years and older without a history of heart attack or stroke.

(doi:10.1001/jama.2016.15450; the full report is available pre-embargo to the media at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) SUNDAY, NOVEMBER 13, 2016

Media Advisory: To contact Michael J. Pencina, Ph.D., email Sarah Avery at sarah.avery@duke.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.13614

The incidence of coronary heart disease in the U.S. declined nearly 20 percent from 1983 to 2011, according to a study appearing in the November 15 issue of JAMA.

Diagnosis and control of coronary heart disease (CHD) risk factors have received particular emphasis in guidelines issued since 1977 (blood pressure) and 1985 (lipids). Yet on a population level, little is known about how these efforts have altered CHD incidence and its association with modifiable risk factors. Michael J. Pencina, Ph.D., of the Duke University Medical Center, Durham, N.C., and colleagues pooled individual patient-level data from 5 observational cohort studies available in the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center. Two analytic data sets were created: 1 set with baseline data collected from 1983 through 1990 (early era) with follow-up from 1996 through 2001, and l set with baseline data collected from 1996 through 2002 (late era) with follow-up from 2007 through 2011.

The study included characteristics of 14,009 pairs of participants in the 2 groups. Participants ages 40 to 79 years who were free of cardiovascular disease were selected from each era and matched on age, race, and sex. Each group was followed for up to 12 years for new-onset CHD (i.e., heart attack, coronary death, angina, coronary insufficiency).

“Examination of adults from 5 large observational cohort studies led to several findings. First, the incidence of CHD declined almost 20 percent over time. Second, although the prevalence of diabetes increased, the fraction of CHD attributable to diabetes decreased over time, due to attenuation of the association between diabetes and CHD. This may have resulted from changing definitions and awareness of diabetes, improvements in diabetes treatment and control, and/or better primary prevention. Third, there was no evidence that the strength of the association between smoking, systolic blood pressure, or dyslipidemia and CHD changed between eras, nor was there evidence that the proportion of CHD due to these factors changed. This underscores the importance of continued prevention efforts targeting these risk factors,” the authors write.

(doi:10.1001/jama.2016.13614; the study is available pre-embargo at the For the Media website)

Editor’s Note: This study was supported by Regeneron and Sanofi Pharmaceuticals. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) FRIDAY, NOVEMBER 11, 2016

Media Advisory: To contact Mark L. Metersky, M.D., email Lauren Woods at lauren.woods@uconn.edu or call 860-987-2116.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16226

In a study published online by JAMA, Mark L. Metersky, M.D., of the UConn School of Medicine, Farmington, and colleagues analyzed trends in Medicare Patient Safety Monitoring System ventilator-associated pneumonia rates from 2005 through 2013.

Whether previously reported decreases in the rates of ventilator-associated pneumonia (VAP) were attributable to better care or stricter application of subjective surveillance criteria is unclear. The Medicare Patient Safety Monitoring System (MPSMS) has independently measured VAP rates since 2005, using a stable definition of VAP. This analysis included MPSMS VAP rates during calendar years 2005 through 2013 among Medicare patients 65 years and older with principal diagnoses of heart attack, heart failure, pneumonia (including a primary diagnosis of sepsis or respiratory failure and a secondary diagnosis of pneumonia), and selected major surgical procedures. The cohort was divided into 4 periods (2005-2006, 2007 and 2009, 2010-2011, and 2012-2013).

The VAP rate was studied among 1,856 patients. The researchers found that the MPSMS VAP rates were stable over time, with an observed rate of 10.8 percent during 2005-2006, 9.7 percent during 2012-2013, and an adjusted average annual change of 0.

“From 2005 through 2013, MPSMS VAP rates remained stable and substantial, affecting approximately 10 percent of ventilated patients. Persistently high VAP rates bolster concerns that most interventions purported to reduce VAP are supported by limited evidence,” the authors write.

(doi:10.1001/jama.2016.16226; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was supported by a contract from the Agency for Healthcare Research and Quality, United States Department of Health and Human Services, Rockville, Md. Qualidigm was the contractor. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 9:30 A.M. (ET) SATURDAY, NOVEMBER 12, 2016

Media Advisory: To contact Atif Rahman, Ph.D., email atif.rahman@liverpool.ac.uk.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.17165

In a study published online by JAMA, Atif Rahman, Ph.D., of the University of Liverpool, England, and colleagues evaluated the effectiveness of a multicomponent behavioral intervention delivered in primary care centers in Peshawar, Pakistan by lay health workers to adults with psychological distress. The study is being released to coincide with its presentation at the International Society for Traumatic Stress Studies annual meeting.

More than 125 million people today are directly affected by armed conflict, the highest number since World War II. Although reported rates of mental disorders vary, a meta-analysis of a subset of relatively rigorous post-conflict surveys showed that mood and anxiety disorders were common, with rates of 17 percent for depression and 15 percent for posttraumatic stress disorder. Scalable interventions to address a range of mental health problems are needed.

In this study, 346 adult primary care attendees with high levels of both psychological distress and functional impairment were randomly assigned to receive 5 weekly 90-minute individual sessions, administered by lay health workers, that included empirically supported strategies of problem solving, behavioral activation, strengthening social support, and stress management (n = 172); or enhanced usual care (n= 174). The trial was conducted from November 2014 through January 2016 in 3 primary care centers in Peshawar, Pakistan.

Among the patients, 146 (intervention) and 160 (enhanced usual care) completed the study. After 3 months of treatment, the intervention group had significantly lower average scores than the control group on measures of anxiety and depression. At 3 months, there were also significant differences in scores of posttraumatic stress, functional impairment, problems for which the person sought help, and symptoms of depressive disorder.

“This randomized clinical trial tested the effectiveness of a brief lay health worker-administered multicomponent intervention in Peshawar, Pakistan, a low-income setting affected by ongoing conflict and insecurity,” the authors write. “Improvement across all dimensions of anxiety, depression, trauma-related symptoms, and functioning demonstrated the effectiveness of the transdiagnostic feature of the intervention.”

(doi:10.1001/jama.2016.17165; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was supported by Elrha’s Research for Health in Humanitarian Crises (R2HC) initiative funded by the UK Department for International Development and the Wellcome Trust. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 8, 2016

Media Advisory: To contact Jonas Bergh, M.D., email jonas.bergh@ki.se.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.15865

Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence-free survival, and nonhematologic toxic effects were more frequent in the tailored dose-dense group, according to a study appearing in the November 8 issue of JAMA.

Dose-dense therapy, defined as delivery of chemotherapy at shorter intervals without increasing the cumulative dose, has been suggested as a means to improve efficacy of chemotherapy for early breast cancer. Dosing of most chemotherapy agents is calculated based on body surface area, which leads to large interpatient variability in toxic effects and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy.

Jonas Bergh, M.D., of the Karolinska Institutet and University Hospital, Stockholm, Sweden, and colleagues randomly assigned 2,017 women who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer to receive tailored dose-dense adjuvant chemotherapy (n = 1,006) or standard chemotherapy (n = 1,011). The study was conducted at 86 sites in Sweden, Germany, and Austria.

Among the randomized patients, 2,000 received study treatment (at least 1 cycle of chemotherapy). Median follow-up time was 5.3 years. The researchers found that the groups did not differ in 5-year breast cancer recurrence-free survival (89 percent [tailored dose-dense group] vs 85 percent [control group]), 5-year overall survival (92 percent vs 90 percent) or 5-year distant disease-free survival (89 percent vs 87 percent). The tailored dose-dense group had significantly better event-free survival (EFS) than the control group (5-year EFS, 87 percent vs 82 percent). Grade 3 or 4 nonhematologic toxic effects occurred in 527 (53 percent) in the tailored dose-dense group and 366 (37 percent) in the control group.

The authors write that an individual patient data meta-analysis would help to assess whether chemotherapy dose intensification in early breast cancer should be reserved for specific subgroups of patients.

(doi:10.1001/jama.2016.15865; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 8, 2016

Media Advisory: To contact Deborah L. O’Connor, Ph.D., R.D., email Suzanne Gold at suzanne.gold@sickkids.ca or call 416-813-7654, ext. 202059.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16144

Among very low-birth-weight (VLBW) infants, the use of supplemental donor milk compared with formula did not improve neurodevelopment at 18 months, according to a study appearing in the November 8 issue of JAMA.

For many VLBW (less than 3.3 lbs.) infants, there is insufficient mother’s milk, and a supplement of pasteurized donor human milk (donor milk) or preterm formula is required. With an increasing awareness of the benefits of mother’s milk, use of donor milk as a supplement has increased substantially in North America. The Human Milk Banking Association of North America estimated that its members dispensed 3.8 million ounces of donor milk in 2015. Despite this shift in practice, there are limited data evaluating the efficacy of “nutrient-fortified” donor milk compared with preterm formula.

Deborah L. O’Connor, Ph.D., R.D., of the Hospital for Sick Children, Toronto, and colleagues randomly assigned VLBW infants to be fed either nutrient-enriched donor milk or formula for 90 days or to discharge when mother’s milk was unavailable. Infants were from 4 neonatal units in Ontario, Canada.

Of 840 eligible infants, 363 (43 percent) were randomized (181 to donor milk and 182 to preterm formula); of survivors, 299 (92 percent) had neurodevelopment assessed. Average birth weight and gestational age of infants was 2.2 lbs. and 28 weeks, respectively, and 54 percent were male. The researchers found that there were no statistically significant differences in average composite scores on measures of cognitive, language, or motor skills between groups.

“If donor milk is used in settings with high provision of mother’s milk, this outcome [neurodevelopment] should not be considered a treatment goal,” the authors write.

The researchers note that a recent systematic analysis of randomized studies found that donor milk as a supplement to mother’s milk did however reduce the risk of necrotizing enterocolitis, a severe gastrointestinal emergency. A similar reduction was found in the current study with the use of nutrient-enriched donor milk.

(doi:10.1001/jama.2016.16144; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was funded by the Canadian Institutes of Health Research and the Ontario Ministry of Health and Long-Term Care. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 8, 2016

Media Advisory: To contact Adam M. Leventhal, Ph.D., email Zen Vuong at zvuong@usc.edu or call 213-740-5277.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.14649

In a study appearing in the November 8 issue of JAMA, Adam M. Leventhal, Ph.D., of the University of Southern California Keck School of Medicine, Los Angeles, and colleagues examined associations of e-cigarette vaping with subsequent smoking frequency and heavy smoking among adolescents.

E-cigarette vaping is reported by 37 percent of U.S. 10th-grade adolescents and is associated with subsequent initiation of combustible cigarette smoking. Whether individuals who vape and transition to combustible cigarettes are experimenting or progress to more frequent and heavy smoking is unknown. In addition, because some adolescents use e-cigarettes as a smoking cessation aid, adolescent smokers who vape could be more likely to reduce their smoking levels over time.

This study consisted of an analysis of data from surveys administered to 10th grade students in ten public high schools in Los Angeles County during the fall (baseline for this report) and spring (6-month follow-up) of 2014-2015. Surveys included e-cigarette and combustible cigarette use questions from prior research, which were used to determine baseline vaping and baseline and follow-up past 30-day smoking frequency and heaviness.

Students with complete vaping and smoking data at baseline and follow-up constituted the analytic sample (n = 3,084; 54 percent girls; baseline average age, 15.5 years). The prevalence rates of past 30-day vaping and smoking were low overall. Smoking frequency at follow-up was proportionately greater with successively higher levels of baseline vaping. Similar trends were found for smoking heaviness.

Adjusting for baseline smoking, each increment higher on the 4-level baseline vaping frequency continuum was associated with proportionally higher odds of smoking at a greater level of frequency and heaviness by follow-up. The positive association between baseline vaping and follow-up smoking frequency was stronger among baseline nonsmokers than baseline infrequent and frequent smokers; similar trends were found for smoking heaviness.

“The role of nicotine and generalizability of these results to other locations and ages, longer follow-up periods, and non-self-report assessments are unknown and merit further inquiry. The transition from vaping to smoking may warrant particular attention in tobacco control policy,” the authors write.

(doi:10.1001/jama.2016.14649; the study is available pre-embargo at the For the Media website)

Editor’s Note: This research was supported by grants from the National Institutes of Health. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 1, 2016

Media Advisory: To contact Seena Fazel, M.D., email seena.fazel@psych.ox.ac.uk.

 
To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.15380

Among released prisoners in Sweden, rates of violent reoffending were lower during periods when individuals were dispensed antipsychotics, psychostimulants, and drugs for addictive disorders, compared with periods in which they were not dispensed these medications, according to a study appearing in the November 1 issue of JAMA.

There were more than 10 million prisoners worldwide in 2015, with approximately 2.2 million in the United States alone. Despite reported decreases in violence in many countries, reoffending rates remain high. From 2005 through 2010, more than one-third of released prisoners in the United States and the United Kingdom were reconvicted of a new crime within 2 years. Most programs to reduce reoffending focus on psychosocial interventions, but their effect sizes are weak to moderate. As psychiatric and substance use disorders, which increase reoffending rates, are overrepresented among jail and prison populations, treatment with appropriate psychotropic medications offers an alternative strategy to reduce reoffending, although there is uncertainty about whether pharmacological treatments reduce reoffending risk.

Seena Fazel, M.D., of the University of Oxford, England, and colleagues examined the associations between major classes of psychotropic medications and violent reoffending. The study included all released prisoners in Sweden from July 2005 to December 2010, through linkage of population-based registers. Rates of violent reoffending during medicated periods (dispensed prescription of psychotropic medications [antipsychotics, antidepressants, psychostimulants, drugs used in addictive disorders, and antiepileptic drugs]) were compared with rates during nonmedicated periods. Prison-based psychological treatments were also included in the analysis.

The study included 22,275 released prisoners (average age, 38 years; 92 percent male). During follow-up (median, 4.6 years), 4,031 individuals (18 percent) had 5,653 violent reoffenses. The researchers found that three classes of psychotropic medications were associated with substantial reductions in violent reoffending: antipsychotics, a 42 percent reduction; psychostimulants, 38 percent; and drugs used in addictive disorders, a 52 percent reduction. In contrast, antidepressants and antiepileptics were not significantly associated with violent reoffending rates.

Analyses also demonstrated that completion of psychological treatments targeting general criminal attitudes and substance abuse was associated with reductions in violent reoffending. The associations with these psychological programs were not stronger than those for medications. “These findings may have implications for risk management, because prison psychological programs need appropriate facilities, require sufficiently trained and supervised therapists, and are likely to be relatively expensive. Provision of medication after prison release needs evaluation as a possibly cost-effective crime reduction alternative. Because prisoners with psychiatric disorders benefit from both pharmacological and psychological treatments, research should investigate whether combining therapies improves outcomes,” the authors write.

“The absolute numbers of prisoners with psychiatric disorders are large worldwide, and most individuals who could benefit from psychotropic treatment do not receive it after prison release. The magnitudes of the associations reported in this study may warrant correctional services to review policies for released prisoners. Evidence-based provision of psychotropic medications to released prisoners may have the potential to make substantial improvements to public health and safety, particularly in countries that are undergoing decarceration [reducing the number of persons imprisoned or the rate of imprisonment].”

(doi:10.1001/jama.2016.15380; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 1, 2016

Media Advisory: To contact Malini DeSilva, M.D., M.P.H., email Vineeta Sawkar at vineeta.s.sawkar@healthpartners.com.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.14432

In an analyses that included more than 300,000 births, tetanus, diphtheria, and acellular pertussis (Tdap) vaccine administration during pregnancy was not significantly associated with increased risk for microcephaly or for structural birth defects in offspring, according to a study appearing in the November 1 issue of JAMA.

In 2012, the U.S. Advisory Committee on Immunization Practices recommended that Tdap vaccine be administered during every pregnancy, ideally between 27 and 36 weeks’ gestation. Previously, Tdap was recommended for unvaccinated pregnant women since 2010 in California and since 2011 across the United States. Cases of microcephaly (an abnormally small head due to failure of brain growth) in Brazil increased substantially during 2015, likely associated with maternal Zika virus infections. However, these cases overlapped with the November 2014 initiation of Brazil’s maternal Tdap program. Previous small observational studies reported no increased risks for birth defects following maternal Tdap vaccination; none focused on microcephaly.

In this study, Malini DeSilva, M.D., M.P.H., of HealthPartners Institute, Minneapolis, and colleagues included data from live births at 7 Vaccine Safety Datalink sites (Northern California, Southern California, Colorado, Minnesota, Oregon, Washington, and Wisconsin) from January 2007 through September 2013 and compared prevalence of structural birth defects between infants born to women who received Tdap during pregnancy and unvaccinated women. Analyses of maternal Tdap vaccination from 27 to 36 weeks’ gestation were limited to 2010-2013 for California sites and to 2012-2013 for other sites. Any structural defect, selected major structural defects, and microcephaly alone were identified from diagnostic codes assigned at medical visits during the first year of life.

Analyses included 324,463 live births. The researchers found that maternal Tdap was not significantly associated with increased risk for microcephaly for vaccinations occurring at less than 14 weeks’ gestation (n = 3,321), between 27 and 36 weeks’ gestation (n = 20,568), or during any week of pregnancy (n = 41,654). Adjusted analyses were similar for any structural birth defect and selected major structural defects.

The authors note that the findings are potentially limited by incomplete data on Tdap vaccinations (making it possible to misclassify women’s immunization status), diagnosed structural birth defects, and important covariates (including maternal alcohol use), as well as inability to study birth defects resulting in pregnancy loss or elective termination.

“The findings support recommendations for routine Tdap administration during pregnancy,” the researchers write.

(doi:10.1001/jama.2016.14432; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was funded by the Centers for Disease Control and Prevention. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) THURSDAY, OCTOBER 27, 2016

Media Advisory: To contact Manisha Juthani-Mehta, M.D., email Ziba Kashef at ziba.kashef@yale.edu or call 203-436-9317. To contact editorial author Lindsay E. Nicolle, M.D., F.R.C.P.C., email Chris Rutkowski at Chris.Rutkowski@umanitoba.ca or call 204-474-9514.

To place an electronic embedded link to these articles in your story  These links will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16141  https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16140

Among older women residing in nursing homes, administration of cranberry capsules compared with placebo resulted in no significant difference in presence of bacteriuria plus pyuria (presence of bacteria and white blood cells in the urine, a sign of urinary tract infection [UTI]), or in the number of episodes of UTIs over l year, according to a study published online by JAMA. The study is being released to coincide with its presentation at IDWeek 2016.

Urinary tract infection is the most commonly diagnosed infection among nursing home residents. Bacteriuria is prevalent in 25 percent to 50 percent of women living in nursing homes, and pyuria is present in 90 percent of those with bacteriuria. Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Manisha Juthani-Mehta, M.D., of the Yale School of Medicine, New Haven, Conn., and colleagues randomly assigned 185 women (average age, 86 years; with or without bacteriuria plus pyuria at study entry) residing in nursing homes to two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (i.e., 72 mg total, equivalent to 20 ounces of cranberry juice) or placebo administered once a day.

Of the 185 study participants (31 percent with bacteriuria plus pyuria at study entry), 147 completed the study. Overall adherence was 80 percent. After adjustment for various factors, there was no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1 percent vs 29.0 percent). There were also no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths), hospitalization, antibiotics administered for suspected UTIs, or total antimicrobial utilization.

“Many studies of cranberry products have been conducted over several decades with conflicting evidence of its utility for UTI prevention. The results have led to the recommendation that cranberry products do not prevent UTI overall but may be effective in older women. This trial did not show a benefit of cranberry capsules in terms of a lower presence of bacteriuria plus pyuria among older women living in nursing homes,” the authors write.

(doi:10.1001/jama.2016.16141; the study is available pre-embargo at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Cranberry for Prevention of Urinary Tract Infection? – Time to Move on

“The continuing promotion of cranberry use to prevent recurrent UTI in the popular press or online advice seems inconsistent with the reality of repeated negative studies or positive studies compromised by methodological shortcomings. Any continued promotion of the use of cranberry products seems to go beyond available scientific evidence and rational reasoning,” writes Lindsay E. Nicolle, M.D., F.R.C.P.C., of the University of Manitoba, Winnipeg, Manitoba, Canada, in an accompanying editorial.

“Some of this conviction is likely an interest of individuals or groups to promote the use of natural health products for clinical benefits, allowing avoidance of medical interventions and, potentially, giving women who experience recurrent UTI an element of personal control in managing their problem. The current emphasis on antimicrobial stewardship and limiting antimicrobial use whenever possible also may have some influence in the continued endorsement of cranberry juice or tablets as a nonantimicrobial strategy for management of UTI.”

“Recurrent UTI is a common problem that is distressing to patients and because it is so frequent and costly for the health care system. It is time to identify other potential approaches for management. This certainly must include a wiser use of antimicrobial therapy for syndromes of recurrent UTI in women in long-term care facilities. Other possible interventions to explore in this and other populations may include, among other approaches, adherence inhibitors or immunologic interventions. Intellectual discussions and clinical trial activity should be redirected to identify and evaluate other innovative antimicrobial and nonantimicrobial approaches. It is time to move on from cranberries.”

(doi:10.1001/jama.2016.16140; the editorial is available pre-embargo at the For the Media website)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 12:30 P.M. (ET) FRIDAY, OCTOBER 28, 2016

Media Advisory: To contact Rafael Harpaz, M.D., M.P.H., email Ian Branam at yfi1@cdc.gov or call 404-639-0316.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16477

In a study published online by JAMA, Rafael Harpaz, M.D., M.P.H., of the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues analyzed data from the 2013 National Health Interview Survey (NHIS; an annual health survey conducted via household interviews) to estimate the prevalence of self-reported immunosuppressed adults in the United States. The study is being released to coincide with its presentation at IDWeek 2016.

The number of immunosuppressed adults in the United States is unknown but thought to be increasing because of both greater life expectancy among immunosuppressed adults due to improvements in medical management, as well as new indications for immunosuppressive treatments. Immunosuppression increases the risks and severity of primary or reactivation infections; its prevalence has implications for food and water safety, tuberculosis control, vaccine programs, infection control strategies, outbreak preparedness, travel medicine, and other facets of public health.

In 2013, NHIS respondents were asked whether they had ever been told by a “doctor or other health professional” that their immune system was weakened. Those responding yes were asked follow-up questions to assess whether that status was current (i.e., at time of response) and to report additional evidence of immunosuppression. Those reporting use of immunosuppressive medications or treatments or occurrence of immunosuppressive medical conditions (i.e., hematopoietic cancers or human immunodeficiency virus [HIV] infection) were considered immunosuppressed in this analysis, but those reporting only frequent colds or infections or attributing immunosuppression solely to chronic diseases or to solid cancers (i.e., in absence of immunosuppressive treatments) were not.

The total 2013 NHIS household response rate was 76 percent, consisting of 41,355 eligible households. Of 34,426 eligible adult respondents within these households, 4.2 percent (n = 1,442) had been told at some time by a health professional that their immune system was weakened. Of these, 2.8 percent (n = 951) reported current immunosuppression and additional evidence of immunosuppression, translating to an estimated U.S. prevalence of 2.7 percent. Prevalence was highest among women, whites, and persons age 50 to 59 years.

“This study was not designed to explore the attributable causes of immunosuppression, although prevalence is likely driven by frequency and chronicity (e.g., life-long immunosuppression due to HIV infection, treatment for autoimmune conditions, or solid organ transplantation vs short-term cancer chemotherapy). The higher prevalence of immunosuppression among women may reflect their higher risk for autoimmune conditions. Age-specific immunosuppression increased with age, in parallel with the epidemiology of prevalent conditions that require immunosuppressive treatments, but it is unclear why it peaked at ages 50 to 59 years,” the authors write.

“This study addresses an underappreciated phenomenon and serves as a call for additional data from other sources to complement and fill the gaps in the study. Tracking immunosuppression over time is particularly important given the hundreds of clinical trials now under way to assess the use of immunosuppressive treatments for prevention or mitigation of common chronic diseases in highly prevalent risk groups.”

(doi:10.1001/jama.2016.16477; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was funded by the U.S. Centers for Disease Control and Prevention. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 25, 2016

Media Advisory: To contact the U.S. Preventive Services Task Force, email the Media Coordinator at Newsroom@USPSTF.net or call 202-572-2044.

To place an electronic embedded link to this report in your story  This link will be live at the embargo time: https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.14697

The U.S. Preventive Services Task Force (USPSTF) recommends providing interventions during pregnancy and after birth to support breastfeeding. The report appears in the October 25 issue of JAMA.

This is a B recommendation, indicating that there is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial.

There is convincing evidence that breastfeeding provides substantial health benefits for children and adequate evidence that breastfeeding provides moderate health benefits for women. However, nearly half of all mothers in the United States who initially breastfeed stop doing so by 6 months, and there are significant disparities in breastfeeding rates among younger mothers and in disadvantaged communities. To update its 2008 recommendation, the USPSTF reviewed the evidence on the effectiveness of interventions to support breastfeeding on breastfeeding initiation, duration, and exclusivity. The USPSTF also briefly reviewed the literature on the effects of these interventions on child and maternal health outcomes.

The USPSTF is an independent, volunteer panel of experts that makes recommendations about the effectiveness of specific preventive care services such as screenings, counseling services, and preventive medications.

Interventions

Primary care clinicians can support women before and after childbirth by providing interventions directly or by referral to help them make an informed choice about how to feed their infants and to be successful in their choice. Interventions include promoting the benefits of breastfeeding, providing practical advice and direct support on how to breastfeed, and providing psychological support. Interventions can be categorized as professional support, peer support, and formal education, although none of these categories are mutually exclusive, and interventions may be combined within and between categories. Interventions may also involve a woman’s partner, other family members, and friends.

Effectiveness of Interventions to Change Behavior

Adequate evidence indicates that interventions to support breastfeeding increase the duration and rates of breastfeeding, including exclusive breastfeeding.

Harms of Interventions to Change Behavior

There is adequate evidence to bound the potential harms of interventions to support breastfeeding as no greater than small, based on the nature of the intervention, the low likelihood of serious harms, and the available information from studies reporting few harms.

Implementation

Not all women choose to or are able to breastfeed. Clinicians should, as with any preventive service, respect the autonomy of women and their families to make decisions that fit their specific situation, values, and preferences.

Summary

The USPSTF found adequate evidence that interventions to support breastfeeding, including professional support, peer support, and formal education, change behavior and that the harms of these interventions are no greater than small. The USPSTF concludes with moderate certainty that interventions to support breastfeeding have a moderate net benefit for women and their children.

(doi:10.1001/jama.2016.14697; the full report is available pre-embargo to the media at the For the Media website)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

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